Magnetic Properties of Thermal Sprayed Tungsten Carbide–Cobalt Coatings

In the information age, the storage and accessibility of data is of vital importance. There are several possibilities to fulfill this task. Magnetic storage of data is a well‐established method and the range of materials used is continuously extended. In this study, the magnetic remanence of thermally sprayed tungsten carbide–cobalt (WCCo)‐coatings in dependence of their thickness is examined. Two magnetic fields differing in value and geometry are imprinted into the coatings and the resulting remanence field is measured. It is found that there are two effects, which in combination determine the effective value of the magnetic remanence usable for magnetic data storage.

     

Reading from computer screen versus reading from paper: does it still make a difference?

Four experiments were conducted to test whether recent developments in display technology would suffice to eliminate the well-known disadvantages in reading from screen as compared with paper. Proofreading speed and performance were equal for a TFT-LCD and a paper display, but there were more symptoms of eyestrain in the screen condition accompanied by a strong preference for paper (Experiment 1). These results were replicated using a longer reading duration (Experiment 2). Additional experiments were conducted to test hypotheses about the reasons for the higher amount of eyestrain associated with reading from screen. Reduced screen luminance did not change the pattern of results (Experiment 3), but positioning both displays in equal inclination angles eliminated the differences in eyestrain symptoms and increased proofreading speed in the screen condition (Experiment 4). A paper-like positioning of TFT-LCDs seems to enable unimpaired reading without evidence of increased physical strain.

Practitioner Summary: Given the developments in screen technology, a re-assessment of the differences in proofreading speed and performance, well-being, and preference between computer screen and paper was conducted. State-of-the-art TFT-LCDs enable unimpaired reading, but a book-like positioning of screens seems necessary to minimise eyestrain symptoms.     

User-centred process for the definition of free-hand gestures applied to controlling music playback

Music is a fundamental part of most cultures. Controlling music playback has commonly been used to demonstrate new interaction techniques and algorithms. In particular, controlling music playback has been used to demonstrate and evaluate gesture recognition algorithms. Previous work, however, used gestures that have been defined based on intuition, the developers’ preferences, and the respective algorithm’s capabilities. In this paper we propose a refined process for deriving gestures from constant user feedback. Using this process every result and design decision is validated in the subsequent step of the process. Therefore, comprehensive feedback can be collected from each of the conducted user studies. Along the process we develop a set of free-hand gestures for controlling music playback. The situational context is analysed to shape the usage scenario and derive an initial set of necessary functions. In a successive user study the set of functions is validated and proposals for gestures are collected from participants for each function. Two gesture sets containing static and dynamic gestures are derived and analysed in a comparative evaluation. The comparative evaluation shows the suitability of the identified gestures and allows further refinement. Our results indicate that the proposed process, that includes validation of each design decision, improves the final results. By using the process to identify gestures for controlling music playback we not only show that the refined process can successfully be applied, but we also provide a consistent gesture set that can serve as a realistic benchmark for gesture recognition algorithms.     

Stochastic Models for Pad Structure and Pad Conditioning Used in Chemical-Mechanical Polishing

Stochastic models are presented for the structure and conditioning of pads used in chemical-mechanical polishing of wafers. First the one-dimensional distribution function of surface depth in the case of a conditioned solid pad is described. Then, for characterizing the structure of a foamed pad, the theory of random closed sets is applied. An important distributional characteristic of a random closed set, the linear contact distribution function, yields the contribution to surface depth resulting from pores. As a special example the Boolean model is considered. This leads to a formula that describes the variability of the surface of a conditioned foamed pad after a certain time. Simulations and experimental data show a good agreement between theory and reality.     

Photopharmacology of Antimitotic Agents

Antimitotic agents such as the clinically approved vinca alkaloids, taxanes and epothilone can arrest cell growth during interphase and are therefore among the most important drugs available for treating cancer. These agents suppress microtubule dynamics and thus interfere with intracellular transport, inhibit cell proliferation and promote cell death. Because these drugs target biological processes that are essential to all cells, they face an additional challenge when compared to most other drug classes. General toxicity can limit the applicable dose and therefore reduce therapeutic benefits. Photopharmacology aims to avoid these side-effects by introducing compounds that can be applied globally to cells in their inactive form, then be selectively induced to bioactivity in targeted cells or tissue during a defined time window. This review discusses photoswitchable analogues of antimitotic agents that have been developed by combining different photoswitchable motifs with microtubule-stabilizing or microtubule-destabilizing agents.     

NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme

In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.     

Isolation of Decidual Macrophages and Hofbauer Cells from Term Placenta—Comparison of the Expression of CD163 and CD80

(1) Background: Placental immune cells are playing a very important role in a successful placentation and the prevention of pregnancy complications. Macrophages dominate in number and relevance in the maternal and the fetal part of the placenta. The evidence on the polarization state of fetal and maternal macrophages involved in both, healthy and pregnancy-associated diseases, is limited. There is no representative isolation method for the direct comparison of maternal and fetal macrophages so far. (2) Material and Methods: For the isolation of decidual macrophages and Hofbauer cells from term placenta, fresh tissue was mechanically dissected and digested with trypsin and collagenase A. Afterwards cell enrichment was increased by a Percoll gradient. CD68 is represented as pan-macrophage marker, the surface markers CD80 and CD163 were further investigated. (3) Results: The established method revealed a high cell yield and purity of the isolated macrophages and enabled the comparison between decidual macrophages and Hofbauer cells. No significant difference was observed in the percentage of single CD163⁺ cells in the distinct macrophage populations, by using FACS and immunofluorescence staining. A slight increase of CD80⁺ cells could be found in the decidual macrophages. Considering the percentage of CD80⁺CD163⁻ and CD80⁻CD163⁺ cells we could not find differences. Interestingly we found an increased number of double positive cells (CD80⁺CD163⁺) in the decidual macrophage population in comparison to Hofbauer cells. (4) Conclusion: In this study we demonstrate that our established isolation method enables the investigation of decidual macrophages and Hofbauer cells in the placenta. It represents a promising method for direct cell comparison, enzyme independently, and unaffected by magnetic beads, to understand the functional subsets of placental macrophages and to identify therapeutic targets of pregnancy associated diseases.     

Hyperinsulinemic Hypoglycemia Associated with a CaV1.2 Variant with Mixed Gain- and Loss-of-Function Effects

The voltage-dependent L-type calcium channel isoform Ca_V1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the Ca_V1.2 α₁-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified Ca_V1.2^L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism.     

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.